神经炎症
小胶质细胞
缺氧诱导因子
高磷酸化
氧化应激
发病机制
缺氧(环境)
神经科学
认知功能衰退
阿尔茨海默病
医学
淀粉样前体蛋白分泌酶
τ蛋白
机制(生物学)
痴呆
疾病
淀粉样前体蛋白
生物
细胞生物学
免疫学
化学
炎症
病理
内分泌学
生物化学
基因
磷酸化
哲学
氧气
认识论
有机化学
作者
Yangyang Wang,Zhicheng Huang,Minghao Yuan,Jing Feng,Ruo-Lan Cai,Qian Zou,Yinshuang Pu,Shengyuan Wang,Fei Chen,Wenmin Yi,Zhang Hui-ji,Zhiyou Cai
摘要
Amyloid-β (Aβ) peptides and hyperphosphorylated tau protein are the most important pathological markers of Alzheimer’s disease (AD). Neuroinflammation and oxidative stress are also involved in the development and pathological mechanism of AD. Hypoxia inducible factor-1α (HIF-1α) is a transcriptional factor responsible for cellular and tissue adaption to low oxygen tension. Emerging evidence has revealed HIF-1α as a potential medicinal target for neurodegenerative diseases. On the one hand, HIF-1α increases AβPP processing and Aβ generation by promoting β/γ-secretases and suppressing α-secretases, inactivates microglia and reduces their activity, contributes to microglia death and neuroinflammation, which promotes AD pathogenesis. On the other hand, HIF-1α could resist the toxic effect of Aβ, inhibits tau hyperphosphorylation and promotes microglial activation. In summary, this review focuses on the potential complex roles and the future perspectives of HIF-1α in AD, in order to provide references for seeking new drug targets and treatment methods for AD.
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